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Adenosine A 1 receptor stimulation inhibits α 1 ‐adrenergic activation of the cardiac sarcolemmal Na + /H + exchanger
Author(s) -
Avkiran Metin,
Yokoyama Hiroyuki
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703647
Subject(s) - adenosine , pertussis toxin , agonist , sarcolemma , medicine , stimulation , endocrinology , chemistry , phenylephrine , receptor , sodium–hydrogen antiporter , adenosine receptor , adenosine a1 receptor , g protein , myocyte , biology , biochemistry , sodium , organic chemistry , blood pressure
Sarcolemmal Na + /H + exchanger (NHE) activity is increased by stimulation of G q protein‐coupled receptors (G q PCRs), but the roles of other GPCRs are largely unknown. We determined the effects of N‐[(1S,trans)‐2‐hydroxycyclopentyl]adenosine (GR79236), a selective agonist of the G i PCR adenosine A 1 receptor, on sarcolemmal NHE activity in adult rat ventricular myocytes ( n =8–10 per group). NHE activity was indexed by the H + efflux rate after intracellular acidification, measured by microepifluorescence. GR79236 alone (0.01–10 μ M ) had no effect on NHE activity. However, co‐administration of GR79236 inhibited, in a concentration‐dependent manner, the stimulation of NHE activity by the α 1 ‐adrenoceptor agonist phenylephrine (10 μ M ). The inhibitory effect of GR79236 (10 μ M ) was abolished by (1) the selective A 1 antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (0.1 μ M ), confirming an A 1 receptor‐mediated action, and (2) pre‐treatment with pertussis toxin (5 μg ml −1 for 60 min), indicating a G i protein‐mediated mechanism. Our data suggest the existence of inhibitory crosstalk between the G i PCR adenosine A 1 receptor and the G q PCR α 1 ‐adrenoceptor in the regulation of sarcolemmal NHE activity. British Journal of Pharmacology (2000) 131 , 659–662; doi: 10.1038/sj.bjp.0703647